CTTI

Final Report

ICH E6 Guideline for Good Clinical Practice – Update on Progress

MAY 18, 2021 TO MAY 19, 2021

CTTI Project: Informing the Update of ICH E6

On behalf of the International Council for Harmonisation (ICH), the ICH E6 Good Clinical Practice (GCP) Expert Working Group (EWG) held a free public web conference to provide an update on the progress to revise this important and impactful guideline. This web conference was convened by the Clinical Trials Transformation Initiative (CTTI).

The EWG held two similar meetings on Tuesday, May 18, 2021 (8-11 a.m. EDT) and Wednesday, May 19, 2021 (6-9 pm JST) to reach a broad global audience across time zones. As you will note on the agenda, the same topics were presented each day with speakers from different regions to represent the global effort. All information and presentations was provided in English.

Recorded presentations of the public web conferences are available above.

Meeting Location:

Virtual Meeting

Meeting Agenda - May 18

Meeting Agenda - May 19

Watch May 18 Web Conference

Meeting Materials:

Video: ICH Guideline Development Process

Watch May 19 Web Conference

Presentations:

Session 1 – General Introduction

Session 2 – E6(R3) GCP Expert Working Group (EWG) Vision & Engagement

Session 3 – Principles & Stakeholder Reflections

Full Web Conference Slide Deck

Additional Meeting Details:

ICH E6 GCP is the international ethical, scientific, and quality standard for the conduct of clinical trials for the development of new drugs and biologics involving human participants that are intended to support regulatory applications. Due to the wide impact of this important guideline, the ICH Management Committee is taking this unique step to provide a status update on the revisions to the guideline.

In this web conference, members of the ICH E6 EWG discussed the work-in-progress to develop principles and annexes for ICH E6 GCP (third version or E6(R3)) that are intended to be responsive across clinical trial types and settings and to remain relevant as technology and methodologies advance. The draft, work-in-progress principles that were made public by the ICH on April 19, 2021, are designed to be flexible and applicable to a broad range of clinical trials. View the principles on the ICH website. The EWG is not taking public comments on the principles at this stage. However, once the ICH E6 guideline achieves step 3 of the ICH guideline development process, the EWG will invite and consider public input.

The EWG also discussed its plans and approaches to update the guideline in general and its engagement efforts with a variety of stakeholders that greatly enriched the discussions of the EWG. As part of these continued efforts to engage with stakeholders, the web conference included presentations from stakeholders on their vision and aspiration for clinical trial design and conduct that are responsive to the needs of the community.

View the full conference agenda here. For additional information on the ICH E6 revision efforts, please see the Reflection Paper on Renovation of Good Clinical Practice and the Concept Paper. For further information on the engagement approach, please see the published outline of the ICH E6 engagement proposal. Other materials, including the current guideline, "ICH E6(R2): Guideline for Good Clinical Practice," the business plan, work plan, an expert list, and reports of prior public engagements are available on the ICH website: https://www.ich.org/page/efficacy-guidelines.

The views and opinions expressed in this presentation are those of the individual presenter and should not be attributed to the Clinical Trials Transformation Initiative, or any organization with which the presenter is employed or affiliated.

Decentralized Clinical Trials Update Expert Meeting

AUGUST 25, 2021 TO AUGUST 26, 2021

CTTI Project: Supporting Decentralized Trial Approaches

Meeting Objectives:

In order to update CTTI’s existing decentralized clinical trials (DCT)* recommendations, this expert meeting aimed to:

Collect recent knowledge and insights – both what works and what doesn’t – from operationalizing DCT solutions (i.e., remote and virtual visits, using local labs and healthcare providers, and direct-to-participant shipping)
Understand current practices for incorporating DCT solutions in clinical trials, including considerations for protocol design and safety monitoring
Identify opportunities to increase adoption of DCT solutions moving forward

*For the purposes of this meeting, DCTs were defined as those executed through telemedicine and mobile/local healthcare providers, using procedures that vary from the traditional clinical trial model (e.g., the investigational medical product is shipped directly to the trial participant).

Meeting Location:

Virtual Meeting

List of Meeting Attendees

Full Presentation Set - Day 1

Full Presentation Set - Day 2

Pre-Meeting Landscape Scan Results

Meeting Materials:

Day 1

Day 2

The views and opinions expressed in these presentations are those of the individual presenter and should not be attributed to the Clinical Trials Transformation Initiative, or any organization with which the presenter is employed or affiliated.

CTTI Data Monitoring Committees Project Expert Meeting

JULY 28, 2015 TO JULY 29, 2015

CTTI Project: Data Monitoring Committees (DMCs)

Meeting Objectives

Present findings and conclusions from the project survey and focus groups
Share and solicit feedback on proposed Data Monitoring Committees (DMCs) recommendations

Meeting Location:

DoubleTree by Hilton Hotel Washington, D.C., Silver Spring, MD

Meeting Materials:

Meeting Presentations:

Click here to view the presentation slides from this meeting.

The views and opinions expressed in this presentation are those of the individual presenter and should not be attributed to the Clinical Trials Transformation Initiative, or any organization with which the presenter is employed or affiliated.

CTTI Antibacterial Drug Development: Statistical Issues Think Tank Meeting

AUGUST 20, 2012

CTTI Project: Unmet Need

Meeting Background:

A CTTI-hosted Statistical Issues Think Tank Meeting was convened to provide an opportunity for leading experts in clinical trial methodologies to discuss alternative approaches to design and analysis that may be useful for antibacterial drug development programs.

Meeting Location:

Bethesda Hyatt Regency, Bethesda, MD

Meeting Materials:

1) Hierarchical nested trial design (HNTD) for demonstrating treatment efficacy of new antibacterial drugs in patient populations with emerging bacterial resistance

Meeting Presentation:

CTTI Statistics Think Tank for Anti-Bacterial Drug Development by Lisa LaVange

Resulting Publications:

On June 23, 2014, Statistics in Medicine published an article by Huque et al. that describes a novel clinical trial model to address the increased prevalence of antibiotic-resistant bacterial infections. This paper resulted from the CTTI-hosted Statistical Issues Think Tank Meeting that author Mohammad Huque attended.

2) The Role of Statistics in Regulatory Decision Making

In February, 2014, this peer-reviewed article was published in Therapeutic Innovation & Regulatory Science. This paper resulted from the CTTI-hosted Statistical Issues Think Tank Meeting where author Lisa M. LaVange, PhD, attended and presented. In this publication, LaVange concludes:

This article presents the author’s view of the important role that statisticians play in regulatory decision making, beginning with a broad overview of current office initiatives, including the development of guidance documents and a recent push for open and transparent collaboration with industry on methods development. Several recent examples are provided to illustrate the impact that statisticians can have on regulatory decisions through the use of strategic quantitative thinking. Also discussed are areas where it is believed that innovative statistical solutions or greater clarity on existing approaches is still needed.

3) Bayesian approach to the design and analysis of non-inferiority trials for anti-infective products

On August 5, 2013, the Journal of Pharmaceutical Statistics published an article by Gamalo et al. that describes a Bayesian approach for the design and analysis of active comparator trials used in the development and market approval of antibacterial drugs. This work was presented in part at the CTTI-hosted Statistical Issues Think Tank Meeting.

“The CTTI Statistics Think Tank, a collaborative initiative with the FDA/CDER Anti-Bacterial Drug Development Task Force, was held in August, 2012 and provided an excellent opportunity for leading statisticians from academia, government, and industry to discuss innovative approaches for accelerating the development of new antibiotics. This article presents a comprehensive Bayesian approach to non-inferiority trials and represents but one of several approaches that were discussed at the Statistics Think Tank meeting. We look forward to additional research being published from the ideas generated at that meeting.” said Lisa LaVange Director of Biostatistics, Food and Drug Administration.

The Bayesian approach may allow for use of information from sources that include observational studies and early phase trials on the effect of the active comparator for study design. This approach may aid in reducing large sample size requirements and decrease study durations for antibacterial agents that enter late-stage clinical development.

The views and opinions expressed in this presentation are those of the individual presenter and should not be attributed to the Clinical Trials Transformation Initiative, or any organization with which the presenter is employed or affiliated.

Developing Effective Quality Systems in Clinical Trials: An Enlightened Approach

OCTOBER 13, 2010 TO OCTOBER 14, 2010

CTTI Project: Quality by Design

Meeting Background:

The Clinical Trials Transformation Initiative (CTTI) has been conducting a project to identify effective and efficient methods to monitor clinical trials. In seeking to identify how best to ensure the reliability of study results and the protection of trial participants, the project team has recognized that quality cannot be “inspected into” a trial but rather must be incorporated from the outset in the trial’s protocol design and operational conduct. To be effective, monitoring should be one component of an overall quality framework that allows potential issues to be identified and addressed as early as possible.

Meeting Objectives:

Describe, discuss, and evaluate novel approaches to clinical trial oversight
Propose an integrated model of quality management that will promote more efficient approaches to design, conduct and oversight of clinical trial
Identify the critical aspects of clinical trials that should be the focus of risk-based approaches to creating quality systems

Meeting Location:

Bethesda Marriott Suites, Bethesda, MD

Meeting Materials:

Meeting Presentations:

CTTI Background by Martin Landray

Defining the Underlying Principles of Quality in Clinical Trials

Quality Design of Trials by Rory Collins
Quality Risk Management in Clinical Trials by Janet Woodcock
Statistical Monitoring Applied to Research Trials by Tomasz Burzykowski

Approaches to Risk-Based Quality Management

Quality by Design/Quality Designs by Beat Widler
Clinical Data Mining as a Basis for an Information-Based Clinical QA Program by Grant Simmons
Quality System Approaches Using Existing Data and Systems by Eileen Magruder
Quality Risk Management Tools by Raffael Jovine
The NIH/NCI Data Quality Initiative by Edward Helton
An Academic Approach: Combining Quality by Design with Central Monitoring by Martin Landray
FDA's Risk-Based Inspection by Leslie Ball
Risk-Based Quality Management of Clinical Trials - A European Regulator's View by Gabriele Schwarz

The views and opinions expressed in this presentation are those of the individual presenter and should not be attributed to the Clinical Trials Transformation Initiative, or any organization with which the presenter is employed or affiliated.

Anti-Bacterial Drug Development: Issues in the Design of Trials in Patients with Unmet Need and in Patients with Hospital-Acquired and Ventilator Associated Bacterial Pneumonia

OCTOBER 11, 2012 TO OCTOBER 12, 2012

CTTI Project: ABDD Unmet Need

Meeting Background:

With rising antibiotic resistance becoming an issue of global concern, the Clinical Trials Transformation Initiative (CTTI) convened a 2-day Antibacterial Drug Development Workshop on October 11-12, 2012 in Crystal City, VA. The workshop is part of a series of expert meetings to explore approaches for accelerating the development of new antibacterial drugs. The two topics of focus for this meeting were exploring a new paradigm for antibacterial drug development in areas of unmet need, and for the treatment of patients with pneumonia that develops in the hospital or while on a ventilator. This workshop followed a think tank on statistical issues that was held on August 20, 2012, in Bethesda, MD, also hosted by CTTI.

There is an urgent need to develop new antibacterial drugs to treat patients with infections caused by bacteria that are resistant to available antibiotics. Antibiotic resistance has been increasing, creating an unmet public health need. This workshop was held in collaboration with FDA’s newly formed Antibacterial Drug Development Task Force within the Center for Drug Evaluation and Research (CDER).

The purpose of the workshop was to understand the challenges in the development of new antibacterial drugs for the treatment of patients with unmet medical need (e.g., patients with multi-drug resistant bacterial infections, who have limited or no options for treatment) and to identify potential solutions that would accelerate the drug development process. Novel endpoints and possible solutions to challenges in trial design for the development of new antibacterial drugs that treat patients with hospital-acquired or ventilator-associated bacterial pneumonia (HABP and VABP) were also explored. A broad range of stakeholders participated in the meeting, including experts from academic institutions, hospitals, pharmaceutical industry, government, and patient advocacy groups.

“The workshop provided an excellent opportunity to discuss new development pathways for antibiotic drugs targeting infections for which we urgently need new antibiotic therapies. Our collaboration with CTTI on this work is part of the CDER Antibacterial Drug Development Task Force’s efforts to accelerate the development of new antibiotics to address critical patient needs”, said Edward Cox, MD, Director of the CDER’s Office of Antimicrobial Products.

Meeting Objectives:

The goal of the first day of the workshop was to define potential pathways and explore new paradigms to accelerate the development of new antibacterial drugs that would address unmet medical need, including discussing acceptable levels of uncertainty related to the risks and benefits of such treatments. The second day focused on issues in clinical trial design including endpoints and operational efficiencies specific to the development of antibacterial drugs for treating patients with hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP).

Meeting Location:

Sheraton Crystal City Hotel, Arlington, VA

Meeting Materials: